The present invention generally relates to implantable drug delivery and electrical stimulation systems and methods, and more particularly relates to utilizing one or more implantable microstimulators for direct electrical current or electrical current pulses along with administration of a specific chemotherapy agent as a therapy for cancer and other neoplastic diseases.
In the year 2000, an estimated 1,220,100 people in the United States were diagnosed with cancer and 552,200 died of this disease. Cancer is actually a group of many related diseases, but all cancers begin with an abnormal cell. The body is made up of many types of cells. Normally, cells grow and divide to produce more cells only when the body needs them. Sometimes, however, cells keep dividing when new cells are not needed. These extra cells form a mass of tissue, called a tumor, or a neoplasm. Tumors may be benign or malignant.
1. Benign tumors are not cancer. They can often be removed and usually do not come back. Cells from benign tumors do not spread to other parts of the body. Most importantly, benign tumors are rarely a threat to life.
2. Malignant tumors are cancer. Cells in these tumors are abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Also, cancer cells can break away from a malignant tumor and enter the bloodstream or the lymphatic system. That is the most common way cancer spreads from the original cancer site to form new tumors in other organs. The spread of cancer is called metastasis.
3. Leukemia and lymphoma are cancers that arise in blood-forming cells. The abnormal cells circulate in the bloodstream and lymphatic system. They may also invade or infiltrate body organs and form tumors.
Most cancers are named for the organ or type of cell in which they begin. For example, cancer that begins in the lung is lung cancer, and cancer that begins in cells in the skin known as melanocytes is called melanoma.
When cancer spreads (i.e., metastasizes), cancer cells are often found in nearby or regional lymph nodes. If the cancer has reached these nodes, then cancer cells may have spread to other organs, such as the liver, bones, or brain. When cancer spreads from its original location to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if lung cancer spreads to the brain, the cancer cells in the brain are actually lung cancer cells. The disease is called metastatic lung cancer.
Cancer Statistics
In men, lung cancer incidence rates have reached an apparent plateau, but prostate cancer has increased dramatically. As a result, cancer of the prostate gland has become the most common type of cancer among both black (incidence rate of 163.1 per 100,000) and white (121.2 per 100,000) males. Lung cancer and colorectal cancer rates are the second and third highest, respectively, for both black and white males.
Breast cancer is by far the most common cancer among both white and black females. It occurs more frequently among white females (113.2 per 100,000) than among black females (94.0 per 100,000). Lung cancer and colorectal cancer are the second and third highest cancers, respectively, among white females compared to ranks of third and second highest, respectively, for black females. Even though lung and colorectal cancers are two of the most common cancers among females, their incidence is much lower than that for males. The fourth most common cancer for both white and black females is uterine cancer.
Treatment
Treatment for cancer can be either local or systemic. Local treatments affect cancer cells in the tumor and the area near it. Systemic treatments travel through the bloodstream, reaching cancer cells all over the body. Surgery and radiation therapy are types of local treatment. Chemotherapy, hormone therapy, and biological therapy are examples of systemic treatment. Healthy cells generally also suffer from the harmful effects of cancer treatment, which may lead to significant side effects.
Surgery includes removal of the cancer and typically some of the surrounding tissue and lymph nodes near the tumor. The side effects of surgery depend on many factors, including the size and location of the tumor, the type of operation, and the patient""s general health.
Radiation therapy (a.k.a. radiotherapy) may be used instead of surgery as the primary treatment for some types of cancer. It also may be given before surgery (a.k.a., neoadjuvant therapy) to shrink a tumor so that it is easier to remove. In other cases, radiation therapy is given after surgery (a.k.a., adjuvant therapy) to destroy any cancer cells that may remain in the area. In addition, radiation may be used alone, or along with other types of treatment, to relieve pain or other problems if the tumor cannot be removed. Radiation therapy can be in either of two forms: external or internal, and some patients receive both.
External radiation comes from a machine that aims the rays at a specific area of the body, and there is no radioactivity left in the body after the treatment.
With internal radiation (also called implant radiation, interstitial radiation, or brachytherapy), the radiation comes from radioactive material in needles, seeds, wires, or catheters and placed directly in or near the tumor. Patients may stay in the hospital while the level of radiation is highest. During the hospital stay, patients may not be able to have visitors or may have only short visits, because patients may be immunocompromised and prone to infection, and because visitors may be exposed to radiation. Implants may be permanent or temporary. The amount of radiation in a permanent implant goes down to a safe level before the person leaves the hospital. The doctor will advise the patient if any special precautions should be taken at home (e.g., avoiding people with infections, care of an implant wound site). With a temporary implant, there is no radioactivity left in the body after the implant is removed.
The side effects of radiation therapy depend on the treatment dose and the part of the body that is treated. Patients are likely to become extremely tired during radiation therapy, especially in the later weeks of treatment. Radiation therapy also may cause a decrease in the number of white blood cells, which are the cells that help protect the body against infection. With external radiation, there may be permanent darkening or xe2x80x9cbronzingxe2x80x9d of the skin in the treated area. In addition, it is common to have temporary hair loss in the treated area, and for the skin to become red, dry, tender, and itchy.
Chemotherapy is the use of drugs to kill cancer cells. One drug or a combination of chemotherapy agents may be used. Chemotherapy may be the only kind of treatment a patient needs, or it may be combined with other forms of treatment. Neoadjuvant chemotherapy refers to drugs given before surgery to shrink a tumor; adjuvant chemotherapy refers to drugs given after surgery to help prevent the cancer from recurring. Chemotherapy also may be used (alone or along with other forms of treatment) to relieve symptoms of the disease.
Chemotherapy is usually given in cycles: a treatment period (one or more days when treatment is given) followed by a recovery period (several days or weeks), then another treatment period, and so on. Most anticancer drugs are given intravenously, some are injected intramuscularly or subcutaneously, and some are given by mouth.
Sometimes the chemotherapy agents are given in other ways. For example, in an approach called intraperitoneal chemotherapy, chemotherapy agents are placed directly into the abdomen through a catheter. To reach cancer cells in the central nervous system (CNS), the patient may receive intrathecal chemotherapy, in which the chemotherapy agents enter the cerebrospinal fluid through a needle placed in the spinal column, or through a device placed under the scalp.
The side effects of chemotherapy depend mainly on the drugs and the doses the patient receives. As with other types of treatment, side effects vary from person to person. Generally, chemotherapy agents affect cells that divide rapidly. In addition to cancer cells, these include red blood cells and white blood cells. When blood cells are affected, patients are more likely to get infections, may bruise or bleed easily, and may feel unusually weak and very tired. Rapidly dividing cells in hair roots and cells that line the digestive tract may also be affected. As a result, side effects may include loss of hair, poor appetite, nausea and vomiting, diarrhea, or mouth sores. Some chemotherapy agents only cause the hair to thin, while others may result in the loss of all body hair. Most side effects go away gradually during the recovery periods between treatments, and hair grows back after treatment is over. Some chemotherapy agents can cause long-term side effects such as loss of fertility.
Hormone therapy is used against certain cancers that depend on hormones for their growth, such as certain types of breast cancer and prostate cancer. Hormone therapy typically consists of drugs that are antagonists to the hormone needed to sustain the growth of the cancer cells, but this treatment may also include the use of drugs that decrease the production or enzymatic conversion of certain hormones. Another type of hormone therapy is surgery to remove organs (such as the ovaries or testicles) that make hormones.
Hormone therapy can cause a number of side effects. Patients may feel tired, have fluid retention, weight gain, hot flashes, nausea and vomiting, changes in appetite, and, in some cases, blood clots. In women, hormone therapy may cause interrupted menstrual periods and vaginal dryness. Hormone therapy in women may also cause either a loss of or an increase in fertility. In men, hormone therapy may cause erectile dysfunction, loss of sexual desire, or loss of fertility. Depending on the drug used, these changes may be temporary, long-lasting, or permanent.
Biological therapy (also called immunotherapy) helps the body""s own immune system to fight cancer or to protect the body from some of the side effects of cancer treatment. Some examples of biological therapy include monoclonal antibodies, interferon (IFN), interleukin-2 (IL-2), and colony-stimulating factors (e.g., G-CSF).
The side effects caused by biological therapy vary with the specific treatment. In general, these treatments tend to cause flu-like symptoms, such as chills, fever, muscle aches, weakness, loss of appetite, nausea, vomiting, and diarrhea. Patients also may bleed or bruise easily, get a skin rash, or have swelling. These problems can be severe, but they go away after the treatment stops.
Drawbacks of available cancer treatments include damage to healthy cells and the resulting significant side effects, such as fatigue, hair loss, hormonal changes that may affect fertility and desire, blood clots, and flu-like symptoms, and/or complex, risky, expensive surgical procedures. What is needed is a therapy for patients with cancer and other neoplastic diseases that is minimally invasive, and provides effective treatment without major side effects.
The invention disclosed and claimed herein addresses the above and other needs and provides implantable, minimally invasive systems and methods for chronically stimulating malignant tumors and other neoplasms with direct electrical current or electrical current pulses, along with administration of a chemotherapy agent(s). Administration of such electrochemotherapy stimulation may provide significant therapeutic benefits in the treatment, control, and/or prevention of cancer and other neoplastic diseases through one or more of a variety of mechanisms discussed below.
A miniature implantable electrical stimulator, such as a Bionic Neuron (also referred to as a BION(copyright) microstimulator) or the like, is provided to treat, via electrochemotherapy, neoplastic diseases such as cancer. The microstimulator may be implanted in a neoplasm via a minimal surgical procedure (e.g., via a small incision and through a cannula, endoscopically, etc.). When synchronized with the administration of a specific chemotherapy agent(s), pulses of electric current and/or a direct electric current will likely be effective in fighting cancer (e.g., by inducing localized necrosis of neoplastic tissue).
The implantable stimulator capable of supplying direct current (DC), electric current pulses, and/or drug infusion used with the present invention possesses one or more of the following properties, among other properties:
at least two electrodes for applying electrical stimulation to surrounding tissue and/or a pump and at least one outlet for delivering a drug or drugs to surrounding tissue;
electronic and/or mechanical components encapsulated in a hermetic package made from biocompatible material(s);
an electrical coil or the like for receiving energy and/or information inside the package, which receives power and/or data by, for instance, inductive or radio-frequency (RF) coupling to a transmitting coil placed outside the body, thus avoiding the need for electrical leads to connect devices to a central implanted or external controller;
means for receiving and/or transmitting signals via telemetry;
means for receiving and/or storing electrical power within the microstimulator; and
a form factor making the microstimulator implantable via a minimal surgical procedure in a target area in the body.
The length and shape of the microstimulator may be varied in order to deliver more effective treatment, e.g., to treat neoplasms of different shapes and sizes. For example, the microstimulator may be a thin cylindrical device with an electrode at each end, or may be a cylindrical device with multiple electrodes along its length and/or circumference, or may be a flat circular device with two or more electrodes distributed around its periphery, or may be a spherical device with two or more electrodes distributed on its surface, or may have any size and configuration suitable for the particular treatment location and stimulation/infusion parameters.
A microstimulator may operate independently, or in a coordinated manner with other implanted microstimulators, other implanted devices, or with devices external to the patient""s body. For instance, a microstimulator may incorporate sensor(s) for sensing a patient""s condition, which information may be used to control electrical and/or drug stimulation parameters in a closed loop manner. The sensing and electrical stimulation capabilities may be incorporated into a single microstimulator; the sensing and drug stimulation capabilities may be incorporated into a single microstimulator; and/or the sensing, electrical stimulation, and drug stimulation capabilities may all be incorporated into a single microstimulator. Alternatively or additionally, a sensor(s) may communicate sensed information to at least one microstimulator with stimulation capabilities, i.e., that can supply a direct electric current and/or electric current pulses, and/or drug infusion.